The proposed research examines the mechanism through which contractility mediates the transmigration of monocytes. The endothelium primarily acts as a physical barrier to enclose the bloodstream. However, it is unclear how leukocytes are able to breach the endothelial barrier and depart from the bloodstream into areas of inflammation. Moreover, dysfunction of the endothelial barrier is a hallmark of atherosclerosis that involves excessive accumulation of macrophages underneath the endothelium and increased endothelial permeability. Based on preliminary data, we hypothesize that the endothelial cells increase contractility in response to monocyte adhesion, and in so doing play an active role in the transmigration process. The proposed research will use both microfabricated tools and molecular biology techniques to investigate the mechanical and biochemical signaling pathways involved within the endothelium during monocyte transmigration. Specifically, we will use a microfabricated device to measure the contractility of the endothelial cells and use molecular methods to measure and control signaling proteins that regulate cytoskeletal tension. This project will provide insight into the molecular mechanisms that control endothelial contractility during transmigration to help advance the understanding of the inflammation process and the development of successful treatments for atherosclerosis. [unreadable] [unreadable] [unreadable]